PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES
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1 PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES OCULAR ONCOLOGY PERIOCULAR CUTANEOUS MALIGNANCY
2 Site Group: Ocular Periocular Cutaneous Malignancies Prepared by: Harmeet S. Gill MD, FRCSC and E. Rand Simpson MD, FRCSC Latest Revision: N. Laperriere, H. Krema 1. INTRODUCTION 3 2. PREVENTION 3 3. SCREENING AND EARLY DETECTION 3 4. DIAGNOSIS 3 5. PATHOLOGY 4 6. MANAGEMENT MANAGEMENT ALGORITHMS SURGERY CHEMOTHERAPY RADIATION THERAPY OTHER THERAPY ONCOLOGY NURSING PRACTICE CLINIC COORDINATION/MANAGEMENT 8 7. SUPPORTIVE CARE PATIENT EDUCATION PSYCHOSOCIAL CARE SYMPTOM MANAGEMENT CLINICAL NUTRITION PALLIATIVE CARE 9 8. FOLLOW-UP CARE 9 Last Revision Date August
3 1. INTRODUCTION Periocular cutaneous malignancies include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sebaceous cell carcinoma (SebCC), and cutaneous malignant melanoma (CMM). Five to 10% of all skin carcinomas occur on the eyelid. BCC is the most common skin cancer to affect the face and frequently involves the periocular region. It accounts for about 90% of malignant eyelid tumors. Although it carries a low metastatic potential, the carcinoma is locally invasive and destructive. Left inadequately treated, BCC can cause extensive tissue damage. This has serious functional and aesthetic implications, particularly when involving the eyelid and face. 2. PREVENTION Smoking cessation and decreasing exposure to UV light (sunscreen, sunglasses, hats) are the most effective strategies to prevent periocular cutaneous malignancy and this is particularly important for fair-skinned persons. Immunocompromised patients must have their immune status optimized. 3. SCREENING AND EARLY DETECTION Patients with a personal or family history of cutaneous malignancy or pre-cancerous skin changes (i.e. actinic keratosis) are encouraged to undergo routine screening for early detection. Those who develop suspicious lesions should be evaluated as soon as possible. Patients with syndromic predisposition to cutaneous malignancy (i.e. xeroderma pigmentosum or basal cell nevus syndrome) are typically evaluated for new lesions every 2 to 6 months. 4. DIAGNOSIS Patients are referred to the Princess Margaret Hospital (PMH) ocular oncology service for localized periocular cutaneous malignancies. Those cases with orbital infiltration, regional or systemic metastasis, or cases co-managed with the PMH Head & Neck Oncology service are also evaluated. Clinical features. Non-melanocytic lesions (BCC, SCC) may demonstrate malignant features including loss of eyelashes, distortion of the eyelid margin architecture, ulceration, pearly borders, telangiectatic vessels, induration, lack of tenderness, bleeding, or evidence of rapid growth. Melanocytic tumors (nevus, melanoma) may increase in size (vertical or radial growth), change in shape, increase in pigmentation, or demonstrate some of the features described above for non-melanocytic lesions. Adnexal lesions (SebCC) may masquerade as chronic, unilateral blepharitis or recurrent chalazion or demonstrate the features described above for nonmelanocytic lesions. Any periocular cutaneous maligancy with orbital infiltration may cause vision loss, exophthalmos with or without double vision, decreased eye motility, or lack of trigeminal sensation. During the initial assessment, a complete ophthalmological examination is performed including Snellen visual acuity, pupil reactivity, colour vision, slit-lamp evaluation, dilated funduscopy, assessment of extraocular motility, periocular and facial skin Last Revision Date August
4 assessment, retropulsion, exophthalmometry, dermatomal trigeminal sensation (V1 and V2), and head and neck lymph node palpation. Ancillary testing. Any evidence of orbital involvement requires orbital neuroimaging (CT and MRI with and without contrast). A metastatic work-up is performed for biopsy-proven SebCC and sentinel lymph node biopsy may be considered for CMM. 5. PATHOLOGY An incisional or excisional biopsy can be performed for non-melanocytic tumors. The specimen is sent in formalin for permanent histopathology. The common histomorphologic features of BCC seen with hematoxylin and eosin (H&E) staining include peripheral palisading, myxoid stroma, and artefactual clefting. Those for SCC include large, polygonal eosinophilic keratinocytes that may transform into nests or keratinous pearls with a surrounding inflammatory infiltrate. Poorly differentiated SCC contains more pleomorphic cells and no keratinization. Pigmented or non-pigmented lesions suspicious for a melanocytic lesion (nevus or melanoma) are best treated by excisional biopsy with 1 to 2mm margins and a notouch technique to avoid spillage of tumor cells. The histologic subtypes of CMM include superficial spreading melanomas, nodular melanomas, lentigo maligna melanomas, acral lentigenous melanomas, and mucosal lentiginous melanomas. More than 70% of CMMs are superficial spreading melanomas with haphazardly distributed atypical melanocytes at all levels of the epidermis. Immunohistochemical markers such as HMB-45 or S-100 are commonly used to confirm the diagnosis. Lesions suspicious for SebCC must be sent fresh so that fat stains such as oil-red-o can be used. Because these tumors can undergo pagetoid spread and commonly have multicentric involvement, map biopsies should be performed. SebCCs may grow in nests with central necrosis and foamy cytoplasm. Sometimes the lesion can mimic BCC, SCC, or a Merkel cell tumor. The TNM classification system for cutaneous malignancy (AJCC, 7 th edition) distinguishes non-eyelid and eyelid tumors. TNM classification for eyelid carcinoma PRIMARY TUMOR (T) FOR EYELID CARCINOMA TX: primary tumor cannot be assessed T0: no evidence of primary tumor Tis: carcinoma in situ T1: tumor less than or equal to 5mm in greatest dimension (not invading the tarsal plate or eyelid margin) T2a: tumor 5-10mm in greatest dimension or any tumor that invades the tarsal plate or eyelid margin Last Revision Date August
5 T2b: tumor 10-20mm in greatest dimension or involves full-thickness eyelid T3a: tumor greater than 20mm in greatest dimension or any tumor that invades adjacent ocular or orbital structures; any T with perineural tumor invasion T3b: complete tumor resection requires enucleation, exenteration, or bone resection T4: tumor is not resectable because of extensive invasion of ocular, orbital, craniofacial structures, or brain REGIONAL LYMPH NODES (N) FOR EYELID CARCINOMA NX: regional lymph nodes cannot be assessed cn0: no regional lymph node metastasis based upon clinical evaluation or imaging pn0: no regional lymph node metastasis based upon lymph node biopsy N1: regional lymph node metastasis DISTANT METASTASIS (M) FOR EYELID CARCINOMA M0: no distant metastasis M1: distant metastasis ANATOMIC STAGE/PROGNOSTIC GROUPS FOR EYELID CARCINOMA Stage 0 Tis N0 M0 Stage IA T1 N0 M0 Stage IB T2a N0 M0 Stage IC T2b N0 M0 Stage II T3a N0 M0 Stage IIIA T3b N0 M0 Stage IIIB Any T N1 M0 Stage IIIC T4 Any N M0 Stage IV Any T Any N M1 Clark staging for cutaneous malignant melanoma Level I: all tumor cells above basement membrane (in situ) Level II: tumor extends into papillary dermis Level III: tumor extends to interface between papillary and reticular dermis Level IV: tumor extends into reticular dermis Level V: tumor invasion of subcutaneous tissue Breslow classification (thickness) for cutaneous malignant melanoma I: less than or equal to 0.75mm II: mm III: mm IV: greater than or equal to 4mm TNM classification for cutaneous malignant melanoma THICKNESS (T) CLASSIFICATION TX: primary tumor cannot be assessed (shave biopsy, regressed primary) Last Revision Date August
6 Tis: melanoma in situ T1: less than or equal to 1.0mm (a: without ulceration and mitosis less than 1/mm2, b: with ulceration and mitosis greater than or equal to 1/mm2) T2: mm (a: without ulceration, b: with ulceration) T3: mm (a: without ulceration, b: with ulceration) T4: greater than 4.0mm (a: without ulceration, b: with ulceration) REGIONAL LYMPH NODE (N) METASTASIS N0: no evidence of regional lymph node metastasis N1: one lymph node (a: micrometastasis clinically occult) (b: macrometastasis clinically apparent) N2: 2 to 3 lymph nodes (a: micrometastasis, b: macrometastasis, c: in transit metastases/satellite(s), without metastatic lymph nodes (N2a: 2-3 nodes positive for micrometastasis; N2b: 2-3 nodes positive for macrometastasis; N2c: in transit met(s)/satellites(s) without metastatic nodes) N3: 4 or more metastatic nodes or matted nodes or in-transit metastases/ satellite(s) with metastatic node(s) DISTANT METASTASIS (M) M0: no evidence of distant metastasis M1a: distant skin, subcutaneous, or nodal metastases, normal serum lactate dehydrogenase (LDH) level M1b: lung metastases, normal LDH level M1c: all other visceral metastases or any distant metastases with an elevated LDH level MELANOMA STAGING Stage 0 Tis N0 M0 Stage IA T1a N0 M0 Stage IB T1b or T2a N0 M0 Stage IIA T2b or T3a N0 M0 Stage IIB T3b or T4a N0 M0 Stage IIC T4b N0 M0 Stage IIIA T1-T4a N1-2a M0 Stage IIIB T1-T4b T1-T4a T1-T4a/b N1-2a N1-2b N2c Stage IIIC T1-T4b N1-2b M0 T1-T4a/b N3 Stage IV Any T Any N M1a-c M0 6. MANAGEMENT 6.1 Management algorithms Last Revision Date August
7 There are many management options for periocular cutaneous malignancies, both surgical and non-surgical. Some non-surgical options include cryotherapy, radiation, photodynamic therapy, electrodissection and curettage, topical 5-fluorouracil, and topical immune modulators such as imiquimod. A problem with non-surgical management, however, is that no pathological specimen is reviewed to ensure complete tumor eradication. 6.2 Surgery The primary management of BCC maybe surgical excision or radiotherapy. Surgical options may include primary excision with predetermined margins, frozen section (FS)-controlled excision, or Mohs micrographic surgery (MMS). The cure rates using these techniques for periocular BCC fall between 85 to 100%. Surgical resection of biopsy-proven SCC or melanoma is commonly performed in collaboration with Mohs surgeons at networked hospitals. The reconstruction is subsequently performed by an oculoplastic surgeon. Tumors with orbital infiltration who are not candidates for radiation treatment may require orbital exenteration. 6.3 Chemotherapy There are many clinical trials underway for novel chemotherapeutic regimens to treat metastatic melanoma with limited efficacy. 6.4 Radiation therapy Eyelid or orbital radiotherapy may be primary treatment for patients where surgical resections will likely be associated with significant tissue deficits, and quite often in elderly patients where comorbid conditions may increase surgical risks, or at patient discretion after consultation with both surgical and radiation teams. Radiation is also used as adjunctive therapy after tumor resection if clear margins are not achieved for an infiltrative, high-risk malignancy (i.e. morpheaform basal cell carcinoma). Eyelid Tumours Immobilization: Simulation: Technique: Energy: Shielding: Dose: neck rest clinical mark up direct apposition with daily topical anesthetic 75, 100, or 225 kv lead cut out for field definition shielding of globe by gold covered lead shields 3500 cgy/5, 4500 cgy/10, 5000 cgy/20, 6000 cgy/30 Orbital Tumours Immobilization: neck rest and thermoplastic shell, relocatable GTC frame Simulation: CT, possibly MRI on occasion Technique: IMRT with daily Image Guidance with cone beam CT Energy: 6 MV Dose: 6000 cgy/30 for primary tumours Last Revision Date August
8 2000 cgy/5, 3000 cgy/10 for metastatic tumours 6.5 Other therapy In January 2012, the US Food and Drug Administration approved the first moleculartargeted therapy for metastatic or locally advanced BCC known as vismodegib (Erivedge). This therapy remains investigational. 6.6 Oncology nursing practice Patients seen at the Ocular Oncology clinic are invariably outpatients. The initial history and assessment of visual acuity and pupil reactivity is performed by the clinic RN. The RN is often used as an initial point of contact by patients when new symptoms develop or other questions arise. 6.7 Clinic Coordination/Management The identification of a specific disease complex and the direction to appropriate subspecialty care is usually accomplished by a trained ocular oncology clinic coordinator/manager (Lee Penney). This individual is frequently an experienced ophthalmic assistant. Knowledge of the vision care referral base and collection of investigational materials for new patients is of paramount importance as first steps to providing optimal patient care. The coordinator also serves an invaluable function in supporting both patient and family during investigation, therapy, and convalescence. 7 SUPPORTIVE CARE 7.1 Patient education Patients and family members are educated on a one-on-one basis by a consultant during the initial assessment and at every follow-up visit. 7.2 Psychosocial care When patients express or display emotional, psychological, or social concerns an effort is made to address these during the clinical encounter. In rare instances when this is insufficient to deal with all issues, the patient may be referred to the Department of Psychosocial Oncology. 7.3 Symptom management Patients with pain, blurry vision, eye redness or discomfort, are treated with topical artificial tears or other medications as needed. 7.4 Clinical nutrition The role of nutritional advice and support in the ocular oncology patient population is very limited. Patients with dry eye syndrome may be educated about the value of omega-3-fatty acid and flax seed intake while those with age-related macular degeneration may be encouraged to eat green leafy vegetables. Last Revision Date August
9 7.5 Palliative care The medical oncology group facilitates end-of-life palliative care as needed. This occurs very rarely for patients with periocular cutaneous malignancy seen by the ocular oncology service. 7.6 Other Many patients travel from across Canada to the Ocular Oncology service of PMH. The clinic makes every effort to accommodate patients based on travel dates and facilitate lodging when required. 8 FOLLOW-UP CARE Most patients are followed for tumor recurrence and functional and aesthetic rehabilitation post-surgery outside of the ocular oncology service at PMH (i.e. private office). Last Revision Date August
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